Verapamil and Norverapamil Plasma Concentrations During Long-Term Therapy in Patients with Hypertrophic Obstructive Cardiomyopathy

Abstract

Plasma concentrations of verapamil and norverapamil were measured with a gas chromatographic method in 31 patients with hypertrophic obstructive cardiomyopathy during long-term maintenance therapy (6 months-5 years) with verapamil. In 20 patients on a maintenance dosage of 480 mg/day, verapamil concentrations approximately 12 hr after the last regular dose were 91 ± 76 ng/ml (mean ± SD) and levels 1 hr after an oral test dose of 160 mg were 355 ± 253 ng/ml. The values before and after the test dose were highly correlated, r = 0.7272 (p < 0.001). The concentration of norverapamil before the test dose in these 20 patients (160 ± 121 ng/ml) showed a strong positive correlation with the corresponding verapamil concentrations. Verapamil and norverapamil did not accumulate in plasma during long-term treatment with 480 mg daily. A 25-fold difference between patients on this dosage was found for verapamil plasma concentrations before the test dose and a 13-fold difference after it. This large interpatient variation may be mainly due to differences in the first-pass metabolism of verapamil. We recommend that verapamil plasma concentrations be measured to guide therapy with this drug.